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The utility and limitations of glycosylated human CD133 epitopes in defining cancer stem cells

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Abstract

Human CD133 (human prominin-1), a five transmembrane domain glycoprotein, was originally identified as a cell surface antigen present on CD34+ hematopoietic stem cells. Although the biological function of CD133 is not well understood, antibodies to CD133 epitopes have been widely used to purify hematopoietic stem and progenitor cells. The cancer stem cell (CSC) hypothesis postulates that a rare population of tumor cells possessing increased capacities for self-renewal and tumor initiation is responsible for maintaining the growth of neoplastic tissue. The expression of the CD133 epitopes, AC133 and AC141, has been shown to define a subpopulation of brain tumor cells with significantly increased capacity for tumor initiation in xenograft models. Following the discovery of the AC133/AC141+ population of brain tumor stem cells, the AC133 and AC141 epitopes have been extensively used as markers for purifying CSCs in other solid tumors. There are, however, several issues associated with the use of the AC133 and AC141 CD133 epitopes as markers for CSCs. The antibodies routinely used for purification of AC133 and AC141-positive cells target poorly characterized glycosylated epitopes of uncertain specificity. Discordant expression of the AC133 and AC141 epitopes has been observed, and the epitopes can be absent despite the presence of CD133 protein. In addition, CD133 expression has recently been shown to be modulated by oxygen levels. These factors, in combination with the uncertain biological role of CD133, suggest that the use of CD133 expression as a marker for CSCs should be critically evaluated in each new experimental system and highlight the need for additional CSC surface markers that are directly involved in maintaining CSC properties.

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Abbreviations

CSC:

Cancer stem cell

mAb:

monoclonal antibody

FACS:

fluorescence-activated cell sorting

aa:

amino acids

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Acknowledgement

We thank the National Institute of Health (R01 CA118919 to BL) and the US Army Medical Research and Material Command (W81XWH-05-1-0027 to BL) for financial support.

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Authors and Affiliations

  1. Department of Anesthesia, University of California at San Francisco, 1001 Potrero Ave., 3C38, San Francisco, CA, 94110, USA

    Scott Bidlingmaier, Xiaodong Zhu & Bin Liu

  2. Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, 94110, USA

    Bin Liu

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  1. Scott Bidlingmaier
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  2. Xiaodong Zhu
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Correspondence to Bin Liu.

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Bidlingmaier, S., Zhu, X. & Liu, B. The utility and limitations of glycosylated human CD133 epitopes in defining cancer stem cells. J Mol Med 86, 1025–1032 (2008). https://doi.org/10.1007/s00109-008-0357-8

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